Integrated Transcriptomics and Metabolomics Analysis

Transcriptomes enable the holistic analysis of gene function and gene structure. This can illuminate the molecular mechanisms underlying certain biological activities and illness. The collection of all metabolites present in a cell at any given time is known as the metabolome. It is composed of tiny molecules that serve as substrates and yield to various metabolic processes. A cell's metabolome can be used to examine its physiological status at sampling. Metabolomics studies can also reflect on its surroundings.

By integrating transcriptomics and metabolomics analysis of biological samples, we can analyze the intrinsic changes of organisms at cause and effect, and can more systematically and comprehensively analyze biomolecular functions and regulatory mechanisms to achieve an understanding of the general trends and directions of biological changes, and then propose models of molecular biological change mechanisms and screen key metabolic pathways or genes and metabolites for subsequent in-depth research and application.

Combined transcriptomic and targeted metabolomic analysis reveals the mechanism of flesh browning in cold stored 'Fuji' apple fruit (Jihan Wang, et al,. 2023)

The significance of combined transcriptomic and metabolomic analysis

Given the complexity and integrative nature of biological processes, it is challenging to systematically and comprehensively resolve the regulatory mechanisms of intricate physiological processes. This is done using data from a single histology. Our combined transcriptome and metabolome analysis service can simultaneously explore biological problems from a more systematic and comprehensive perspective, validate each other, and screen key genes, metabolites and metabolic pathways to deeply analyze the macro developmental processes of biological systems and better explain the complexity and integrality of biological processes.

Sample preparation for combined transcriptomic and metabolomic analysis

The combined transcriptomic and metabolomic analysis is a single sample sent to both histologies, and the combined multi-omics analysis requires a large sample size preparation. Three biological replicates are recommended for general transcriptomics. In contrast, metabolomics is based on multivariate statistical analysis and requires more replicates than transcriptomics, with at least six biological replicates recommended for a single sample. Biological replicates can not only eliminate intra-group errors, but also serve as quality control points to determine whether the experimental design process is abnormal, and detect outlier samples to avoid the risk of experimental failure.

What are the content of combined transcriptomes and metabolomics analysis?

• Transcriptome differential gene bioinformatics analysis.
• Differential metabolite bioinformatics analysis.
• Metabolic pathway-based integration analysis.
• Metabolite-related enzyme and differential gene integration based analysis.

Our service workflow

Our technical advantages

• Comprehensive data. Using comprehensive transcriptomic data and the latest metabolomic database, we are able to comprehensively analyze the interrelationship between transcriptome and metabolome.
• Linkage analysis. Integrating transcriptomic and metabolomic data, we can dig deeper into the genes and metabolites involved in the regulatory process to reveal the real gene expression regulatory network.
• Project experience. We have proven research portfolio solutions to help users publish their research results quickly.

What do we offer?

Creative Proteomics will provide you with a detailed technical report on the following.

• Experimental steps.
• Relevant experimental parameters.
• Mass spectrometry images.
• Raw data.
• Transcriptomics and metabolomics analysis results.

Creative Proteomics has rich multi-omics co-analysis experience. Our advanced sequencing platform ensures the ability to detect the overall transcript level of any species at the single nucleotide level. We also combine transcriptome sequencing results with metabolomic analysis services based on multiple technologies,enabling targeted and untargeted metabolomic analysis of multiple samples. If you are interested in us, please feel free to contact us.

Reference

1. Jihan Wang, Fujun Li, Xinyue Zhang, et al. Combined transcriptomic and targeted metabolomic analysis reveals the mechanism of flesh browning in cold stored 'Fuji' apple fruit. Scientia Horticulturae, 2023;320:112195.

Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis

Journal: Gastroenterology

Published: 2021

Abstract

Alcoholic hepatitis (AH) is characterized by loss of hepatocyte dedifferentiation and maturation. Glucose metabolism is tightly regulated in healthy hepatocytes. In this article, the authors provide a rationale for the possibility that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism. They perform comprehensive metabolomic and transcriptomic analyses of liver tissues from patients with AH or alcoholic cirrhosis, or normal liver tissues after hepatectomy.

Results

There were 206 metabolites that distinguished the AH and AC cohorts from the control cohort (Figure 1B), consistent with the similar etiology of these alcohol-induced chronic liver diseases. Importantly, 58 metabolites (24 increases and 34 decreases) were uniquely altered in AH patients compared with control individuals, and 22 metabolites were uniquely altered between the AH and AC cohorts. The metabolites that were significantly altered in the AH involved amino acid, carbohydrate, vitamin, energy, and nucleotide metabolism. (Figure 1C, yellow annotation). These changes in hepatic metabolite levels define the AH-specific metabolite profile.

Figure 1

Further exploring changes in gene expression of enzymes involved in intermediary metabolism, the authors focused on genes encoding enzymes of glycolysis, gluconeogenesis, TCA cycle, glycogen metabolism, and and monosaccharide and disaccharide metabolism. Significantly lower mRNA expression levels were found for all of the identified enzymes involved in glycogen metabolism, including glycogen synthase, which catalyzes the rate-limiting step of glycogen synthesis, and glycogen phosphorylase, which catalyzes the rate-limiting step of glycogen breakdown. Importantly, the mRNA expression levels of only 8 enzymes were significantly altered in AC compared with controls, suggesting that the dysregulation of intermediary metabolic gene expression is specific to AH(Figure 2).

Figure 2

The authors examined expression changes and correlations between genes and metabolites associated with glycolysis, gluconeogenesis, and the TCA cycle through a comprehensive systems biology analysis. Using a network-based approach, several possible metabolite libraries were identified, including G6P, acetyl-CoA, and citrate. The increased abundance of these metabolites in the AH compared to control samples was accompanied by a decrease in downstream intermediates, suggesting the presence of multiple localized sites of metabolite accumulation. The TCA cycle, in particular, showed significantly reduced levels of several metabolites, suggesting that normal hepatic energetic processes are disrupted by the AH in favor of alternative pathways, such as triglyceride synthesis and the pentose phosphate pathway (Figure 3 A). In addition, the authors performed a correlation analysis between gene expression and metabolite changes. We found no significant correlation between AH and control samples (Figure 3 B). Comprehensive analysis of dirty metabolomics and transcriptomics revealed reprogramming of glucose metabolism in alcoholic hepatitis, and dysregulation of glucose metabolism may lead to abnormalities in liver function in AH by altering storage/release mechanisms, use of alternative energy pathways, and metabolic depots and bottlenecks.

Figure 3

Conclusion

The authors integrated the results of transcriptomic and metabolomic analyses and found that altered metabolite levels and metabolizing enzyme messenger RNA expression suggest extensive reprogramming of glucose metabolism in AH. Increased expression of HKDC1 may lead to a dysregulation of glucose metabolism and represent a novel biomarker and therapeutic target for AH.

Reference

1. Massey V, Parrish A, Argemi J, et al,. Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis. Gastroenterology. 2021 Apr;160(5):1725-1740.e2.